MAO Inhibitors

[Nestran]

Below is taken from the New Zealand study of the Ruyan carts. Am I reading this correct in that it seems to be saying that cigarettes contain inhibitors that enhance the effect of nicotine??? If so, just how addictive IS Nicotine? Like caffeine, maybe a bit worse?

2.3 Monoamine oxidase​

.​

Rationale.​

MAO, an enzyme naturally found in blood platelets and the brain, metabolises
dopamine, also known as the pleasure drug. When this process is inhibited by known
MAO inhibitors in tobacco smoke, dopamine tends to accumulate, reinforcing the effect
of nicotine. The question is whether e-cigarette cartridge liquid also acts to inhibit MAO
and reinforce the addictive effect of nicotine, or whether it acts like pure nicotine.​

Method.​

Samples of the liquid contained in the Ruyan e-cigarette cartridges were tested
with a monoamine oxidase (MAO) enzyme activity assay which employs the fluorescent
MAO substrate kynuramine, and the effect compared with that from tobacco extracts
including a nicotine-free tobacco.​

Laboratory.​

ESR Porirua NZ, a Crown Research Institute.​

Results.​

Monoamine oxidase (MAO) enzymes both A and B, were strongly inhibited by
tobacco smoke extracts but the cartridge liquid alone had no such effect15.​

Conclusion.​

The Ruyan E-cigarette cartridge liquid does not behave like a tobacco
extract. The absence of a MAO inhibitor effect means the e-cigarette has no detectable​

addictive potential beyond that of nicotine.

 

[Zofryer]

My understanding of the MAO inhibitors is their function is to enhance nicotine absorption rather than some direct effect on neuroreceptors. So it's not making the nicotine more addictive per say, but instead making it more effective. So a cheap way for them to get more bang for the buck.

I could be completely and totally wrong though.

 

[Basil]

MAO inhibitors are a group of old drugs used to treat depression.

They have a lot of interactions with other drugs, which is why they are rarely used nowadays.

Their presence in real smoke and absence from vapor may explain some of the withdrawal when switching from analogs. Nice find that.

 

[TropicalBob]

This is perhaps the biggest reason why e-smoking does NOT satisfy so many, no matter the nicotine strength of the cart/liquid. We have numerous posts from the past on "what is missing".

 

[happily]

I'd say nicotine is not as addicting as we think... Some days I vape less than 10mg and hardly touch the e-cig(if I'm busy) and some days I vape 36mg like crazy. I was a 2-3 pack a day smoker and the only way I vape more is if I am doing absolutely nothing. It feels more like snacking than smoking to me now. I'll soon be cutting almost all my liquids to low nic.

 

[TropicalBob]

That's the best thing you can do. I'm a heavy nicotine addict and cannot rely on e-cigs to satisfy my needs. For that, I use snus, dissolvables, nasal snuff and a pipe.

 

[gatsby]

Its all dopamine regulation whether you are directly or indirectly exciting the release, depressing the re-uptake, or affecting the breakdown of dopamine. we all just what a lot of dopamine hanging around those receptors. It makes you feel good.

 

[Corksil]

Someone already said it but mao inhibitors (as far as I know) allow certain chemicals to bind with them and pass through the blood-brain barrier. I never knew tobacco companies put maoi's in cigarettes - but it makes perfect sense to me now.

without them - trace amounts of nicotine would cross the blood/brain barrier (get inside your mind) -- but w/maoi's in the body, more nicotine would make it to the brain - thus getting more of an affect (more happy nicotine feelings.)

clever companies - but the downside is that lots of other chemicals can get into the brain w/maoi's in the bloodstream. For instance chemicals in food that you would naturally metabolize in a healthy way end up in the brain wreaking havoc w/fragile brain chemistry.

the real question is - could maoi's be used to potentiate the nicotine in e-cig vapor? I think the answer is yes, but I'm not bold enough to try. The stronger the maoi's - the stronger the nicotine effect would be, but the riskier and more dangerous. I've heard stories of ppl taking maoi's for other things (like depression) and ending up in the hospital getting their stomachs filled w/charcoal (soaks up toxins in the body) and stumbling home the next day wondering what happened w/a $3000 hospital bill in one hand.

Anyone feel like taking maoi's and smoking e-cigs? If so drop me a PM and tell me how it went. (there are lots of naturally occurring maoi's found in nature such as harmaline which you take w/ayhuasca to feel trippy and psychedelic.)

 

[DaBrat]

It has long been the practice of Big tobacco to include additives to make their product more addictive. Yes manipulating checmicals to act as MAO inhibitors would strengthen this effect. IT has also been long thought that the nicotine ALONE was not the deciding factor in nicotine addiction in tobacco smoking. I have read many studys about MAO inhibitors in tobacco smoke (not sure if it is a characteristic of the plant itself).

The reaction of the two is what keeps the addiction to cigarettes so hard to break. IT seems that the ecig has managed to remove the one factor, while giving the brain the nicotine, it does not enhance the crave and reward as much which may explain why heavy smokers, like myself can do fine on lower than expected doses of nicotine in our liquid.

Has anyone noticed that when you want to drag on your ecig, you simply want it? With cigarettes I HAD to have it. Complete with nervousness and all after a long outing. I am cutting my liquid to nearly 0 and the only problem I have with it is lack of throat hit. I truly believe I could go 0 with a decent throat hit. Gonna try mixing VG and menthol and a couple of other tips I have read here to see if it can be done. Throat hit is very significant in my addiction.

 

[Casey C]

Its all dopamine regulation whether you are directly or indirectly exciting the release, depressing the re-uptake, or affecting the breakdown of dopamine. we all just what a lot of dopamine hanging around those receptors. It makes you feel good.

word.

Someone already said it but mao inhibitors (as far as I know) allow certain chemicals to bind with them and pass through the blood-brain barrier. I never knew tobacco companies put maoi's in cigarettes - but it makes perfect sense to me now.

It has long been the practice of Big tobacco to include additives to make their product more addictive. Yes manipulating checmicals to act as MAO inhibitors would strengthen this effect. IT has also been long thought that the nicotine ALONE was not the deciding factor in nicotine addiction in tobacco smoking. I have read many studys about MAO inhibitors in tobacco smoke (not sure if it is a characteristic of the plant itself).

wrong, and wrong

MAOIs act by inhibiting the activity of monoamine oxidase, thus preventing the breakdown of monoamine neurotransmitters and thereby increasing their availability. There are two isoforms of monoamine oxidase, MAO-A and MAO-B. MAO-A preferentially deaminates serotonin, melatonin, epinephrinenorepinephrine. MAO-B preferentially deaminates phenylethylamine and trace amines. Dopamine is equally deaminated by both types. Many formulations have forms of fluoride attached to assist in permeating the blood-brain barrier, which is suspected as a factor in pineal gland effects.

Technically, nicotine is not significantly addictive, as nicotine administered alone does not produce significant reinforcing properties. However, only after co-administration with an MAOI, such as those found in tobacco, nicotine produces significant behavioral sensitization, a measure of addiction potential.

The only 599 things U.S. tobacco companies are allowed to add to cigarettes are approved food additives

List of additives in cigarettes - Wikipedia, the free encyclopedia

MAOI's are their own drug, if you want some go tell your doctor

 

[dragonpuff]

Correct me if i'm wrong, but don't MAO inhibitors occur naturally in tobacco?

I quit smoking less than a week ago, but i've always thought that if time proves it to be difficult, taking a low-dose MAOI would be worth a try.

 

[tiffytiff]

if i am reading this right . this may explain the bout of depression i am currently coming out of. my last smoke was aug. 3rd. and i think i cried for an the entire week of the 10th. maybe it was completely unrelated, maybe not, i do feel fine now, but was a bit depressed for a couple of weeks.........hmmmm

 

[Casey C]

Correct me if i'm wrong, but don't MAO inhibitors occur naturally in tobacco?

yeah that's part of what I was pointing out

On a grander scale, its not like tobacco companies are some evil corporate giant out to kill people. Tobacco has been smoked since 5000B.C., they're just providing the service of growing and rolling it for people, they didn't invent the cigarette..

 

[breno]

That's the best thing you can do. I'm a heavy nicotine addict and cannot rely on e-cigs to satisfy my needs. For that, I use snus, dissolvables, nasal snuff and a pipe.

Just those 4?
I find I need ...... ....... and crack to get the same effect

 

[breno]

Below is taken from the New Zealand study of the Ruyan carts. Am I reading this correct in that it seems to be saying that cigarettes contain inhibitors that enhance the effect of nicotine??? If so, just how addictive IS Nicotine? Like caffeine, maybe a bit worse?

2.3 Monoamine oxidase​

.​

Rationale.​

MAO, an enzyme naturally found in blood platelets and the brain, metabolises
dopamine, also known as the pleasure drug. When this process is inhibited by known
MAO inhibitors in tobacco smoke, dopamine tends to accumulate, reinforcing the effect
of nicotine. The question is whether e-cigarette cartridge liquid also acts to inhibit MAO
and reinforce the addictive effect of nicotine, or whether it acts like pure nicotine.​

Method.​

Samples of the liquid contained in the Ruyan e-cigarette cartridges were tested
with a monoamine oxidase (MAO) enzyme activity assay which employs the fluorescent
MAO substrate kynuramine, and the effect compared with that from tobacco extracts
including a nicotine-free tobacco.​

Laboratory.​

ESR Porirua NZ, a Crown Research Institute.​

Results.​

Monoamine oxidase (MAO) enzymes both A and B, were strongly inhibited by
tobacco smoke extracts but the cartridge liquid alone had no such effect15.​

Conclusion.​

The Ruyan E-cigarette cartridge liquid does not behave like a tobacco
extract. The absence of a MAO inhibitor effect means the e-cigarette has no detectable​

addictive potential beyond that of nicotine.

Interesting... I had looked up the effects of cigarettes before on wiki and was very surprised not only does it act like a MAOI inhibitor, which is and antidepressent it also enhances the effects of serotonin, now there is another class of anti-depressants called SSRI's specific seretonin re-uptake inhibitors, effective they also enhance the effects of serotonin just like a cigarette!! They also enhance opiate activity and act like amphetamine!!

So basically you have got the whole doctors cabinet in a cigarette, and their was me, reluctant to take anti-depressants for anxiety perscribed by my doctor because "I didn't want all those chemicals 'taking my mind' away"!

It's also weird that you have to get all that stuff on a perscription yet you can walk into a newsagent and buy a packet of cigarettes no problem as long as you hand over the cash. Also you don't get a leaflet with a list of side effects as long as your arm, it was amusing so see 'death' 8-o listed casually alooongside 'dry mouth'

On a side note you mention caffine as if it is not very addictive, but have your every tried giving it up?

 

[breno]

Erowid Nicotine Vault : Dosage

Research actually looking at the blood plasma of Cigarette smokers has shown that up to 3.0mg of nicotine may be received from a single cigarette. (Benowitz 1998)

"the average from using the historical method was 0.90mg/cigarette while the average from the Massachusetts method was 1.89mg/cigarette."

 

[ladyraj]

Rationale.
MAO, an enzyme naturally found in blood platelets and the brain, metabolises dopamine, also known as the pleasure drug. When this process is inhibited by known MAO inhibitors in tobacco smoke, dopamine tends to accumulate, reinforcing the effect of nicotine. The question is whether e-cigarette cartridge liquid also acts to inhibit MAO and reinforce the addictive effect of nicotine, or whether it acts like pure nicotine.

My response:

If an MAO is what metabolizes dopamine...wouldn't an inhibitor prevent the dopamine being metabolized?

Once an accumulation occurred what triggers the release? Cessation of the inhibitor.

If tobacco prevented dopamine metabolization woulded you feel the pleasure once the effects were removed and dopamine stabilized?

 

[breno]

Rationale.
MAO, an enzyme naturally found in blood platelets and the brain, metabolises dopamine, also known as the pleasure drug. When this process is inhibited by known MAO inhibitors in tobacco smoke, dopamine tends to accumulate, reinforcing the effect of nicotine. The question is whether e-cigarette cartridge liquid also acts to inhibit MAO and reinforce the addictive effect of nicotine, or whether it acts like pure nicotine.

My response:

If an MAO is what metabolizes dopamine...wouldn't an inhibitor prevent the dopamine being metabolized?

Once an accumulation occurred what triggers the release? Cessation of the inhibitor.

If tobacco prevented dopamine metabolization woulded you feel the pleasure once the effects were removed and dopamine stabilized?

This is how I see it, sort of, dopamine is the pleasure chemical, when something makes you happy you produce dopamine, now it is not normal to be permantly happy so MAO breaks it down so you feel normal again.

Thats what happens, you get paid or whatever or win a prize and you feel happy, eventually it wears off as the dopamine wears off, thats why money alone or whatever won't make you happier than anyone else, the initial effect wears off. Now even when nothing special happens your brain produces some dopamine to give you a reasonale level of 'contentness', now if you smoke the chemicals inhibit the metabolism of dopamine so it builds ups much in the same was as if the brain released it because you were happy.
When you stop smoking the dopamine is metabolised again so you feel less happy, further more as your brain has got used to high levels of dopamine you might not feel as happy as if you had never smoked.
Infact you might feel like you had lost your job!!

Sort of analogy say unhappyess if the hight of your arm, pres your arms against as wall for a while so you are now happy, however take the wall away (the cigarette) and you notice you arm will rise up ie you become very unhappy!!

Thats the addictive nature of drugs I think, your body adapts to the prop
and when you take it away you feel worse than when you first started!! (unfortunbately).
Thats why drugs in general don't work in the long term, what works best for such things is CBT, cognative behaviour therapy, apparently. However it is easier to smoke or for the doctor to give you a pill.

 

[gatsby]

Rationale.
MAO, an enzyme naturally found in blood platelets and the brain, metabolises dopamine, also known as the pleasure drug. When this process is inhibited by known MAO inhibitors in tobacco smoke, dopamine tends to accumulate, reinforcing the effect of nicotine. The question is whether e-cigarette cartridge liquid also acts to inhibit MAO and reinforce the addictive effect of nicotine, or whether it acts like pure nicotine.

My response:

If an MAO is what metabolizes dopamine...wouldn't an inhibitor prevent the dopamine being metabolized?

Once an accumulation occurred what triggers the release? Cessation of the inhibitor.

If tobacco prevented dopamine metabolization woulded you feel the pleasure once the effects were removed and dopamine stabilized?

Basically dopamine is released in your brain at various levels all the time and when it contacts a receptor you feel happy (thats a really really gross over simplification but it does the job). What doesn't attach to the receptors is slurped up by other receptors or metabolized. The goal of most of these chemicals (nicotine, some anti-depressants, .......) is to keep the receptors unnaturally washed in dopamine in one of three ways; excite the release of more dopamine, inhibit the re-up-take, or inhibit the metabolizing enzymes. Its al the same to your brain. Of course this is a natural process throughout the day in response to things like good food, sex, sky diving etc. and if you continue to over do it unnaturally you cause damage and need your fix in other ways. Hence addicts like us.

 

[Mister]

I've been reading a fair bit about the biochemical aspects of cigarette addiction.

In what I've read two things stand out to me so far:

Speed of effect:

Nicotine can enter the body in two chemical forms: free-base, or as a salt. Many modern cigarettes deliver a fair bit of free-base nicotine. All current non-burning forms of delivery (patch, snus, vaping, etc.) deliver only the salt form. Free-base nicotine reaches the brain receptors much more quickly.

The maximum effect from a puff on a cigarette occurs in 10 to 20 seconds.

The maximum effect from a puff on an e-cig occurs in about a minute.

I suspect that this difference is a large part of the "what's missing" question.

I hope that someone who understands these things may one day (soon!) find a way for e-juice to deliver free-base nicotine to our systems, without adding anything harmful to accomplish this. That might result in super-vapor which has less or nothing missing.

Spectrum of addiction:

It seems that the processing of nicotine may physically change the brain in such a way that it creates physical addiction to activities associated with the nicotine consumption. This could partially explain the success of vaping as an alternative to smoking.

Vaping allows us to continue numerous associated actions - the throat hit, seeing the vapor, the hand and oral activity, etc. Smokers may have developed a physical need (addiction) for some of these things as much as their need for nicotine.

A note regarding the addiction mechanisms involved:

This is so complex that it is only partially understood.

Nicotine is definitely central to the mechanism, and nicotine's direct action on neural receptors is well understood. Uptake rates, metabolism of nicotine, half-life, and storage in other cells is all also fairly well understood.

The consequences of blocking the receptors involved are very complex and not at all well understood. It is currently considered probable, but not certain, that dopamine is a strong player in the next stage of the mechanism.